Project Summary: The Harvard-MIT Division of Health Sciences and Technology (HST) proposes to continue its successful training program in Bioinformatics and Integrative Genomics (BIG). This program addresses the growing gap between the ability to generate copious amounts genomic data and the ability to systematically and efficiently make sense of all this data. This program seeks to train competent, multidisciplinary researchers who are capable of both integrating the technologies into their experimental investigations and synthesizing the resulting datasets into coherent knowledge frameworks and mathematical models for formulating and resolving fundamental questions in biology and medicine. The BIG training program draws on three significant strengths of the local academic environment: the breadth of talented investigators at Harvard, MIT, and affiliated hospitals, the rich variety of quantitatively oriented courses in advanced genomics-bioinformatics offered at Harvard and MIT, and the template of HST's Medical Engineering and Medical Physics (MEMP) PhD program. As new track within MEMP, the BIG pre-doctoral program provides training in biomedical sciences and pathophysiology, as well as a formal introduction to clinical medicine. This proposal includes two main elements: the continuation of the predoctoral BIG training program established in 2001 and full institutionalization of the highly successful Summer Institute in Bioinformatics piloted in 2005. The Summer Institute is a key element of the plan to attract talented undergraduates, particularly women and underrepresented minorities, to the emerging field of genomics. Relevance: Perhaps the most important short-to-midterm translational aspect of bioinformatics and genomics is the ability to identify populations at risk for a variety of gene-by-environment interacting diseases. This includes morbid obesity and its frequent sequelae such as diabetes mellitus. This population-based risk stratification is an important first step in focusing primary prevention efforts as the most cost-effective way to lower the national disease burden. Given the significant representation of BIG faculty engaged in precisely this area of population-based risk stratification, and the large proportion of BIG students working with them, this aspect of public health and primary prevention is particularly well addressed by the training program.